title: Intraperitoneal infusion of paclitaxel with S-1 for peritoneal metastasis of advanced gastric cancer: phase I study.
abstract: BACKGROUND
  Intraperitoneal administration of taxanes revealed excellent anti-tumor effect for peritoneal metastasis of gastric cancer in some experimental models. The aim of this study is to determine maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended dose (RD) of intraperitoneally infused paclitaxel (PTX) with S-1 as a phase I study.
  
  
  METHODS
  Eighteen patients with advanced gastric cancer in addition to confirmed peritoneal metastasis using laparoscopy were enrolled in this study. The regimen consists of oral administration of S-1 (Dose 80 mg: BSA<1.25 m(2), 100 mg: 1.25<BSA<1.5 m(2), 120 mg: BSA>1.5 m(2)) for 14 days and intraperitoneal infusion of PTX (Dose escalation: level I: 40, II: 60, III: 80, level IV: 90, V: 100 mg/m(2)) at day 1 and 14. PTX concentrations in serum and ascites were determined at 4, 8, 12, 24, 48 hours after the infusion, which was repeated twice every 4 weeks.
  
  
  RESULTS
  The number of patients were as follows: Level I: 3, Level II: 6, Level III: 3, Level IV: 3, Level V: 3. Grade 3 leukocytopenia was confirmed in 1 (Level II) and 2 (Level V). MTD is 90 mg/m(2), RD is 80 mg/m(2) and DLT is Grade 3 leukocytopenia. The average serum PTX concentrations remained in optimal range except for all 3 of level V patients. In all cohorts, the PTX concentrations in the ascites were approximately 1000 folds higher than those in serum for 48 hours after the infusion.
  
  
  CONCLUSIONS
  MTD and RD were PTX 90 mg/m(2), 80 mg/m(2), respectively. These findings were supported by pharmocokinetics of PTX.
authors.affiliation: Department of Digestive Surgery and Transplantation, Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Masanori
authors.initials: M
authors.lastname: Nishioka
authors.forename: Shinya
authors.initials: S
authors.lastname: Morimoto
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Jun
authors.initials: J
authors.lastname: Higashijima
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Miyatani
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nakao
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001202:Ascitic Fluid / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D017239:Paclitaxel